Changing eye color by gene transduction

Abstract

A person's iris color can lighten, such as from brown to lighter brown, green, hazel, or blue, by introducing a melanocyte-killing agent through the cornea of the person's eye and contacting the anterior surface of the iris with the agent at a dose sufficient to kill melanocytes in the iris stroma.

What is claimed is: 
     
       1. A composition in a unit dose for changing a color of a subject's iris of an eye, comprising: a sterile ophthalmic preparation comprising a genetic vector comprising (a) a suicide gene; and (b) a melanocyte-specific gene promoter operably linked to the suicide gene, wherein the unit dose is sufficient to kill melanocytes in a stroma of the subject's iris of the eye without inducing visible inflammatory cells or flares in the anterior chamber of the eye. 
     
     
       2. The composition in the unit dose of  claim 1 , wherein the genetic vector is selected from the group consisting of a plasmid, an adenovirus, an adeno-associated virus, and a lentivirus. 
     
     
       3. The composition in the unit dose of  claim 1 , wherein the genetic vector comprises a recombinant adeno-associated virus. 
     
     
       4. The composition in the unit dose of  claim 1 , wherein the sterile ophthalmic preparation is in a powder form, and is reconstitutable with a fluid to form a sterile ophthalmic solution or suspension. 
     
     
       5. The composition in the unit dose of  claim 1 , further comprising a biocompatible object comprising the sterile ophthalmic preparation and sized to be placed in contact with a person's the subject's iris. 
     
     
       6. The composition in the unit dose of  claim 5 , wherein the biocompatible object comprises a disc, strip, or pledget. 
     
     
       7. The composition in the unit dose of  claim 1 , wherein the suicide gene is selected from the group consisting of (i) a herpes simplex virus thymidine kinase (HSVtk) gene; (ii) a cytosine deaminase gene; (iii) a nitroreductase gene; and (iv) a carboxypeptidase G2 gene. 
     
     
       8. The composition in the unit dose of  claim 1 , wherein the melanocyte-specific gene promoter comprises a tyrosinase (Tyr) promoter. 
     
     
       9. The composition in the unit dose of  claim 1 , wherein the suicide gene comprises a HSVtk gene, and the melanocyte-specific gene promoter comprises a Tyr promoter. 
     
     
       10. The composition in the unit dose of  claim 1 , wherein the unit dose comprises 5-50 μL of the sterile ophthalmic preparation comprising 1E10 to 1E13 vector genomes (vg)/ml of the genetic vector. 
     
     
       11. The composition in the unit dose of  claim 1 , wherein the sterile ophthalmic preparation is suitable for injection directly into the anterior chamber of the eye. 
     
     
       12. A pharmaceutical composition for changing a color of a subject's iris of an eye, comprising:
 a sterile ophthalmic preparation comprising an effective dose of a genetic vector comprising (a) a suicide gene; and (b) a melanocyte-specific gene promoter operably linked to the suicide gene, 
 wherein the effective dose is sufficient to: change color of the subject's iris of the eye and kill melanocytes in a stroma of the subject's iris of the eye without inducing visible inflammatory cell or flare in the anterior chamber of the eye, after the pharmaceutical composition is injected directly into the anterior chamber of the eye. 
 
     
     
       13. The pharmaceutical composition of  claim 12 , wherein the genetic vector is selected from the group consisting of a plasmid, an adenovirus, an adeno-associated virus, and a lentivirus. 
     
     
       14. The pharmaceutical composition of  claim 12 , wherein the genetic vector comprises a recombinant adeno-associated virus. 
     
     
       15. The pharmaceutical composition of  claim 12 , wherein the sterile ophthalmic preparation is in a powder form, and is reconstitutable with a fluid to form a sterile ophthalmic solution or suspension. 
     
     
       16. The pharmaceutical composition of  claim 12 , wherein the suicide gene is selected from the group consisting of (i) a herpes simplex virus thymidine kinase gene; (ii) a cytosine deaminase gene; (iii) a nitroreductase gene; and (iv) a carboxypeptidase G2 gene. 
     
     
       17. The pharmaceutical composition of  claim 12 , wherein the melanocyte-specific gene promoter comprises a Tyr promoter. 
     
     
       18. The pharmaceutical composition of  claim 12 , wherein the suicide gene comprises a HSVtk gene, and the melanocyte-specific gene promoter comprises a Tyr promoter. 
     
     
       19. The pharmaceutical composition of  claim 12 , wherein the effective dose comprises 5-50 μL of the sterile ophthalmic preparation comprising 1E10 to 1E13 vector genomes (vg)/ml of the genetic vector.